This Alzheimer's Disease Research Center continues to focus upon research that can illuminate basic mechanisms underlying the development of adult dementing disorders, with particular attention to heritable susceptibility factors underlying Alzheimer's Disease (AD). Five research projects are concerned with: 1) the genetic analysis of different sub-groups of AD; 2) the role of glucocorticoids in neurotoxicity and cognitive decline in aged nonhuman primates and clinical investigations of the role of the hypothalamic-pituitary axis in the pathogenesis of AD; 3) the role of perlecan, a high molecular weight heparin sulfate proteoglycan, in the genesis of AD; 4) attempts to develop transgenic mouse models of AD- related pathology based upon overexpression of a C-terminal domain of the human beta amyloid precursor protein and postulated interactions with the protein products of allelic variants of the human Apolipoprotein E gene; 5) investigations of the neurotrophic effects of estrogens in the aging brain of Fischer 344 rats and related studies using human post-mortem brain tissue. The following Core Units support the above and other AD- related research projects at this University: A) Administration; B) Research Training and Information Transfer; C) Clinical; D) General Autopsy and Neuropathology; E) Cell Tissue and Fluid Bank, Cell Culture and Cytogenetics; F) Data management; G) Molecular Genetic Analysis Core. The Clinical Registry Core is supplemented by a Satellite Core devoted to underserved populations of this region. Funds are also required for the support of pilot projects by faculty members of the University of Washington and affiliated institutions.